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From the Departments of Anaesthesiology and Biostatistics, Sanjay Gandhi Postgraduate Institute of Medical Sciences, Lucknow, India.
Address correspondence to: Dr. Chandra Kant Pandey, Associate Professor, Department of Anaesthesiology, Sanjay Gandhi Postgraduate Institute of Medical Sciences, Lucknow 226014, India. Phone: 91-522-440715 or 719, ext. 2490; Fax: 91-522-440017, 440078, attention to Dr. C. K. Pandey; E-mail: ckpandey{at}sgpgi.ac.in
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Abstract |
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Methods: 320 ASA I and II patients, non-smokers of both sexes scheduled for elective surgery between the ages of 18 to 60 yr were randomly allocated into four equal groups. The patients were assigned to receive lidocaine 0.5 mg·kg–1 (Group I), 1.0 mg·kg–1(Group II), 1.5 mg·kg–1 (Group III) or placebo (Group IV) over five seconds, one minute prior to the administration of fentanyl 3 µg·kg–1 in a randomized and double-blind fashion. Any episode of cough was classified as coughing and graded as mild (1–2) moderate (3–4) or severe (5 or more). The data were analyzed by test of proportion.
Results: Eleven, 12, 11 and 28 patients (13.75%, 15%, 13.75% and 35%) had cough in Groups I, II, III and IV respectively (P < 0.05 Groups I, II, III vs IV). There was no significant difference in the incidence and severity of cough among the lidocaine pretreated groups (P > 0.05).
Conclusion: The results of our study suggest that iv lidocaine 0.5 mg·kg–1 is the minimal dose required to suppress fentanyl-induced cough when administered one minute prior to fentanyl. Any further increase in the lidocaine dose does not reduce the incidence or severity of fentanyl-induced cough.
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Introduction |
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Intravenous lidocaine suppresses the cough reflex during endotracheal intubation, extubation, bronchography, bronchoscopy and laryngoscopy.5–7 It has been found effective when given intravenously to suppress the cough reflex of endotracheal intubation and cough induced by manual displacement of the endotracheal tube and instillation of distilled water into the trachea in anesthetized patients.8–10 In a placebo-controlled clinical study it has been demonstrated that lidocaine 1.5 mg·kg–1 decreased fentanyl-induced cough from 34.22% to 13.14% (absolute risk reduction was 21.08% and relative risk reduction was 62%) one minute prior to fentanyl administration.11 We evaluated the minimal dose of lidocaine for suppression of fentanyl-induced cough in this randomized, prospective and placebo-controlled study.
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Material and methods |
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All patients received a premedication with oral lorazepam 0.04 mg·kg–1 the evening before surgery and in the morning one hour prior to surgery. In the operating room venous access was established on the dorsum of the non-dominant hand and an electrocardiogram, noninvasive blood pressure and pulse oximeter were applied. Patients were randomly assigned into four groups using a computer generated table of random numbers to receive iv lidocaine 0.5 mg·kg–1 (Group I), 1.0 mg·kg–1 (Group II) or 1.5 mg·kg–1 (Group III) or placebo (Group IV) over five seconds one minute prior to the iv administration of fentanyl 3 µg·kg–1. Any episode of cough was classified as coughing. An observer, unaware of the type of medication given to the patients, recorded the number of episodes of coughing, if any. Severity of coughing was graded based on the number of episodes of cough (mild 1–2, moderate 3–4 and severe 5 or more).
Considering the incidence of coughing following peripherally administered iv fentanyl is 30%, and assuming a reduction of 20% (assumption based on the results of a previous clinical investigation)11 at the 5% level of significance and 80% confidence of detecting a true difference following lidocaine treatment, a minimum of 79 patients was required in each group. After completion of the study, the treatment groups were decoded and the data were entered into the statistical software package SPSS 9.0 (Chicago, IL, USA). The demographic data were compared by one-way ANOVA and Chi-square test. Comparison between the groups was performed for overall incidence of cough by test of proportion (Z test) and severity of cough by Fisher Exact test. A P value < 0.05 was considered statistically significant.
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Results |
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). Eleven, 12 and 11 patients (13.75%, 15% and 13.75%) had cough in Groups I, II, and III respectively. Twenty-eight patients (35%) of Group IV had cough (P < 0.05; Table II). There was no significant difference in the severity of cough among the groups (P > 0.05; Table II).
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Discussion |
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). The incidence of cough in the placebo group (IV) was 35%, higher than in previous reports (28%).1,3 The higher incidence of fentanyl-induced cough in our study is probably because of a larger dose of fentanyl (3 µg·kg–1) compared to the studies by Agarwal et al. (2 µg·kg–1) and Phua et al. (1.5 µg·kg–1).1,4 A 46% incidence of cough has been reported with 7 µg·kg–1 fentanyl administered through a central venous catheter over one second by Bohrer et al., whereas the same incidence was reported by Lui et al. with 5 µg·kg–1 administered through a peripheral vein over five seconds.3,12 Intravenous lidocaine administration has been shown to suppress both mechanical and chemical induced airway reflexes, including the cough reflex.5,6,8–10 The dose of lidocaine required for the effective suppression of cough during tracheal intubation ranges between 1.5 to 2.0 mg·kg–1 and the duration of cough suppression was reported to last about five to eight minutes in previous studies.5,9,10 The effect of iv lidocaine on suppression of cough during endotracheal intubation increased in a dose-dependent manner and correlated well with plasma levels. Administration of iv lidocaine 2.0 mg·kg–1 one to five minutes before intubation suppressed the cough reflex significantly in a group of patients under nitrous oxide-halothane anesthesia whose ages ranged between 15 to 55 yr and who did not receive a muscle relaxant.10 In our previous study we evaluated the effect of lidocaine on fentanyl-induced cough with a fixed dose of 1.5 mg·kg–1. Lidocaine 1.5 mg·kg–1 administered one minute prior to fentanyl significantly reduced the incidence of cough from 34.22% to 13.14% (absolute risk reduction of 21.08% and relative risk reduction of 62%).11 In the present study we used increasing doses of lidocaine to evaluate its suppressive effect on fentanyl-induced cough. The results demonstrate that all doses reduced the incidence of cough, but that there is no significant difference between treatment groups.
The mechanisms of fentanyl-induced cough are not well understood but various theories have been proposed. Fentanyl has been shown to inhibit central sympathetic outflow causing vagal predominance, inducing cough and reflex bronchoconstriction.1,12,13 Effective suppression of the cough response from 43% to 3% after terbutaline and salbutamol (selective beta2-adrenergic bronchodilator) inhalation supports the concept of bronchoconstriction.12 The rapid response of the reflex and efficacy of morphine in preventing cough suggests that a pulmonary chemoreflex is also the likely mechanism, mediated by either irritant-receptors (rapidly adapting receptors) or by vagal C fibre receptors in close proximity to pulmonary vessels (juxta capillary receptors). On the other hand, suppression of cough with betamethasone inhalation supports the trigger stimulus and bronchial hyperirritability theory.1,2,12 Histamine release from mast cells in the lungs (though this appears unlikely as fentanyl rarely causes histamine release) or constriction of the tracheal smooth muscles (by release of tachykinins from sensory nerve endings due to citrate in fentanyl citrate) and the possible stimulation of irritant receptors following deformation of the tracheobronchial wall triggering the cough are other plausible explanations.1,3,14,15
The mechanisms by which lidocaine suppresses cough are not known but it has been proposed that depression of brain stem functions by lidocaine may be responsible for cough suppression. An alternate mechanism is that lidocaine may act by anesthetizing peripheral cough receptors in the trachea and hypopharynx.8
In conclusion, our study suggests that iv lidocaine 0.5 mg·kg–1 is the minimal dose to suppress fentanyl-induced cough when administered one minute prior to fentanyl. Any further increase in the lidocaine dose does not reduce the incidence and severity of fentanyl-induced cough.
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Footnotes |
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References |
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2 Tweed WA, Dakin D. Explosive coughing after bolus fentanyl injection. Anesth Analg 2001; 92: 1442–3.
3 Bohrer H, Fleischer F, Werning P. Tussive effect of a fentanyl bolus administered through a central venous catheter. Anaesthesia 1990; 45: 18–21.[Medline]
4 Phua WT, Teh BT, Jong W, Lee TL, Tweed WA. Tussive effect of a fentanyl bolus. Can J Anaesth 1991; 38: 330–4.
5 Yukioka H, Yoshimoto N, Nishimura K, Fujimori M. Intravenous lidocaine as a suppressant of coughing during tracheal intubation. Anesth Analg 1985; 64: 1189–92.
6 Smith FR, Kundahl PC. Intravenously administered lidocaine as cough depressant during general anesthesia for bronchography. Chest 1973, 63: 427–9.
7 Baraka A. Intravenous lidocaine controls extubation laryngospasm in children. Anesth Analg 1978; 57: 506–7.
8 Poulton TJ, James FM III. Cough suppression by lidocaine. Anesthesiology 1979; 50: 470–2.[Medline]
9 Nishino T, Hiraga K, Sugimori K. Effects of i.v. lignocaine on airway reflexes elicited by irritation of the tracheal mucosa in humans anaesthetized with enflurane. Br J Anaesth 1990; 64: 682–7.
10 Yukioka H, Hayashi M, Terai T, Fujimori M. Intravenous lidocaine as a suppressant of coughing during tracheal intubation in elderly patients. Anesth Analg 1993; 77: 309–12.[Medline]
11 Pandey CK, Raza M, Ranjan R, et al. Intravenous lidocaine suppresses fentanyl-induced coughing: a double-blind, prospective, randomized placebo-controlled study. Anesth Analg 2004; 99: 1696–8.
12 Lui PW, Hsing CH, Chu YC. Terbutaline inhalation suppresses fentanyl-induced coughing. Can J Anaesth 1996; 43: 1216–9.
13 Yasuda I, Hirano T, Yusa T, Satoh M. Tracheal constriction by morphine and by fentanyl in man. Anesthesiology 1978: 49: 117–9.[Medline]
14 Stellato C, Cirillo R, de Paulis A, et al. Human basophil/mast cell releasability. IX. Heterogeneity of the effects of opioids on mediator release. Anesthesiology 1992; 77: 932–40.[Medline]
15 Ricciardolo FL. Mechanisms of citric acid-induced bronchoconstriction. Am J Med 2001; 111: 18S–24S.
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